Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

中文翻译：

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新的MYO15A变体与伊朗的两个家谱有听力障碍

非综合征性听力损失（NSHL）的临床遗传诊断非常具有挑战性。关于其高度异质性以及某些基因的大尺寸，使用传统方法检测因果突变也确实很困难。因此，已在这一领域开发了一种称为全外显子组测序（WES）的最新技术，以消除常规方法的局限性。这项研究是对两个不相关谱系与多个受影响的听力损失病例（HL）进行研究研究的报告。因此，两个家族都进行了临床评估和遗传分析。在本研究中报道了WES数据分析的结果，以揭示常染色体隐性非综合征性听力损失（ARNSHL）致病变异。初步分析确定了MYO15A iecT6442A：p的两个新颖变体。W2148R和c.10504dupT：p.C3502Lfs * 15相应地被后来的Sanger验证和偏析分析所证实。根据在线预测工具，两个已识别的变体似乎都具有破坏作用。在这项研究中，完整的外显子组测序被用作识别两个伊朗ARNSHL家族MYO15A的两个新变异的第一种方法策略。